TY - JOUR
T1 - Synthesis-free PET imaging of brown adipose tissue and TSPO via Combination of Disulfiram and <sup>64</sup>CuCl<sub>2</sub>
JF - bioRxiv
DO - 10.1101/131193
SP - 131193
AU - Yang, Jing
AU - Yang, Jian
AU - Wang, Lu
AU - Moore, Anna
AU - Liang, Steven H.
AU - Ran, Chongzhao
Y1 - 2017/01/01
UR - http://biorxiv.org/content/early/2017/04/26/131193.abstract
N2 - PET imaging is a widely applicable but a very expensive technology. Strategies that can significantly reduce the high cost of PET imaging are highly desirable both for research and commercialization. On-site synthesis is one important contributor to the high cost. In this report, we demonstrated the feasibility of a synthesis-free method for PET imaging of brown adipose tissue (BAT) and translocator protein 18kDa (TSPO) via a combination of Disulfiram, an FDA approved drug for alcoholism, and 64CuCl2 (termed 64Cu-Dis). Our blocking studies, Western blot, and tissue histological imaging suggested that the observed BAT contrast was due to 64Cu-Dis binding to TSPO, which was further confirmed as a specific biomarker for BAT imaging using [18F]-F-DPA, a TSPO-specific PET tracer. Our studies, for the first time, demonstrated that TSPO could serve as a potential imaging biomarker for BAT. Furthermore, since imaging contrast obtained with both 64Cu-Dis and [18F]-F-DPA was not dependent on BAT activation, these agents could be used for reliably imaging BAT mass. Additional value of our synthesis-free approach could be applied to imaging TSPO in other tissues as it is an established biomarker of neuro-inflammation in activated microglia and plays a role in immune response, steroid synthesis, and apoptosis. Although here we applied 64Cu-Dis for a synthesis-free PET imaging of BAT, we believe that our strategy could be extended to other targets while significantly reducing the cost of PET imaging.Significance Brown adipose tissue (BAT) has been considered as “good fat,” and large-scale analysis has undoubtedly validated its clinical significance. BAT tightly correlates with body-mass index (BMI), suggesting that BAT bears clear significance for metabolic disorders such as obesity and diabetes. BAT imaging with [18F]-FDG, the most used method for visualizing BAT, primarily reflects BAT activation, but not BAT mass. A convenient imaging method that can consistently reflect BAT mass is still lacking. In this report, we demonstrated that BAT mass can be reliably imaged with a synthesis-free method using the combination of Disulfiram and 64CuCl2 (64Cu-Dis) via TSPO binding. We further demonstrated for the first time that TSPO is a specific imaging biomarker for BAT.
ER -